Hyperthermia is one of the oldest clinically applied agents enhancing the effectiveness of various anti-cancer therapies. Hyperthermia is a type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs (cyclophosphamide, doxorubicin, cisplatin, etoposide, ifosfamide, gemcitabine, interferon-alpha, vincristine, carboplatin, oxaliplatin . . . ). It is generally not used alone. The studies have focused on the treatment of many types of cancer, including sarcoma, melanoma, head and neck, brain, lung, esophagus, breast, bladder, rectum, liver, cervix and peritoneal mesothelium. However, the exact mode of action of hyperthermia remains elusive.
WO 2010/082821 and Krawczyk et al (2011, Proc Natl Acad Sci) disclose that mild hyperthermia inhibits homologous recombination (HR) and induces BRCA2 degradation. Homologous recombination is one of pathways to repair of double-stranded break (DSB). It is known that BRCA2 is involved in recombinational repair of double-stranded break (DSB) and that PARP inhibitors are effective in killing BRCA2-defective breast cancer cells. Therefore, the authors postulated that an agent inducing DSBs may be used for treating cancer while simultaneously inhibited BRCA2 (and then homologous recombination) by hyperthermia. They also suggested further using a PARP inhibitor with this combination. PARP is involved in the detection and signaling single strand DNA breaks (SSB) to the enzymatic machinery involved in the SSB repair. These authors finally observed that the increase of sensitivity to radiotherapy by hyperthermia is specific of homologous recombination since this effect was not observed in cells deficient for homologous recombination (Rad54−/−).
Even if cancer treatment with hyperthermia is progressing, there is still a strong need for improved methods of cancer treatments using hyperthermia.